Despite their relatively low prevalence, vascular diseases of the liver represent a significant h... more Despite their relatively low prevalence, vascular diseases of the liver represent a significant health problem in the field of liver disease. A common characteristic shared by many such diseases is their propensity to cause portal hypertension together with increased morbidity and mortality. These diseases are often diagnosed in young patients and their delayed diagnosis and/or inappropriate treatment can greatly reduce life expectancy. This article reviews the current body of evidence concerning Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia, cirrhotic portal vein thrombosis and other rarer vascular diseases including arterioportal fistulas. It also includes a section on the diagnostic imaging of vascular diseases of the liver and their treatment from a haematological standpoint (study of thrombotic diathesis and anticoagulation ther...
Portal hypertension is a severe, almost unavoidable complication of chronic liver diseases and is... more Portal hypertension is a severe, almost unavoidable complication of chronic liver diseases and is responsible for the main clinical consequences of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is currently the best available method to evaluate the presence and severity of portal hypertension. Clinically significant portal hypertension is defined as an increase in HVPG to >or=10 mmHg; above this threshold, the complications of portal hypertension might begin to appear. Measurement of HVPG is increasingly used in clinical hepatology, and numerous studies have demonstrated that the parameter is a robust surrogate marker for hard clinical end points. The main clinical applications for HVPG include diagnosis, risk stratification, identification of patients with hepatocellular carcinoma who are candidates for liver resection, monitoring of the efficacy of medical treatment, and assessment of progression of portal hypertension. Patients who experience a reduction in HVPG of >or=20% or to <12 mmHg in response to drug therapy are defined as 'responders'. Responders have a markedly decreased risk of bleeding (or rebleeding), ascites, and spontaneous bacterial peritonitis, which results in improved survival.
NCX-1000 (2(acetyloxy) benzoic acid-3(nitrooxymethyl)phenyl ester) is an nitric oxide (NO)-releas... more NCX-1000 (2(acetyloxy) benzoic acid-3(nitrooxymethyl)phenyl ester) is an nitric oxide (NO)-releasing derivative of ursodeoxycholic acid (UDCA), which showed selective vasodilatory effect on intrahepatic circulation in animal models of cirrhosis. This study was aimed at testing the efficacy and tolerability of this compound in patients with cirrhosis and portal hypertension. This was a single-center, phase-2a, randomized (4:1), double-blind, parallel-group, dose-escalating study. Patients received progressive oral doses of NCX-1000 or placebo up to 2 g t.i.d. or maximum tolerated doses for 16 days. Efficacy on fasting and postprandial hepatic venous pressure gradient (HVPG) at baseline and after treatment was assessed. Hepatic blood flow (HBF) and arterial blood pressure were also measured. Eleven patients (nine NCX-1000 and two placebo) were enrolled and completed the trial. After NCX-1000 treatment, HVPG did not change (16.7+/-3.8 vs. 17.1+/-3.8 mm Hg; P=0.596), and HBF decreased significantly (904+/-310 vs. 1,129+/-506 ml/min; P=0.043). The postprandial increase in portal pressure and HBF was not modified by NCX-1000. There was no significant effect on diastolic blood pressure, but systolic blood pressure was reduced by the treatment in a dose-dependent manner (121+/-11 mm Hg after NCX-1000 vs. 136+/-7 mm Hg at baseline; P=0.003). Seven non-serious adverse events were experienced by four patients (one on placebo). In patients with cirrhosis and portal hypertension, NCX-1000 administration was safe, but it was not able to reduce portal pressure. A significant reduction of systolic blood pressure and HBF was observed in the treatment arm, suggesting that the drug had systemic effects and lacked selective release of NO at the intrahepatic circulation.
Portal hypertension is a major cause of morbidity and mortality in liver cirrhosis. This article ... more Portal hypertension is a major cause of morbidity and mortality in liver cirrhosis. This article provides a background on the most important aspects of the evaluation of portal hypertension in patients with chronic liver diseases, with special attention to the measurement of portal pressure by hepatic vein catheterization. The rationale, technique, applications, costs, and limitations of measurements of the hepatic venous pressure gradient are thoroughly reviewed. Emerging, noninvasive methodologies for the evaluation of the patient with portal hypertension are also discussed.
The purpose of this article is to describe the Doppler waveform findings in the hepatic artery in... more The purpose of this article is to describe the Doppler waveform findings in the hepatic artery in the early posttransplantation period, both in the absence and presence of arterial complications. The presence of transient high-resistance Doppler waveforms in normal hepatic arteries is a common finding after grafting. Hepatic artery thrombosis and stenosis, and arterial steal syndromes can be diagnosed by Doppler in the early liver transplantation period.
We aimed to develop a model based on noninvasive variables for the prediction of clinically signi... more We aimed to develop a model based on noninvasive variables for the prediction of clinically significant portal hypertension (CSPH) and of esophageal varices (EV) in patients with compensated liver disease. Sixty patients with compensated liver cirrhosis diagnosed by histology were included in the training set. All patients had physical examination, laboratory tests, abdominal color-Doppler ultrasound, upper digestive tract endoscopy, and measurement of hepatic venous pressure gradient. Predictive models for the presence of CSPH and of EV were calculated. The models were validated in an independent series of 74 patients with compensated liver disease. Clinical and laboratory variables were selected in the final models, while ultrasonography did not add statistical power for the prediction of CSPH and EV. The model for prediction of CSPH included albumin, INR, and ALT. The best cutoff had 93% sensitivity and 61% specificity in the training set, and correctly classified 77% of patients in the validation set. Spider angiomas, ALT, and albumin predicted EV. The best cutoff of the model in the training set had a sensitivity of 93% and a specificity of 37% and correctly classified 72% of cases in the validation set. Noninvasive prediction of EV in well-compensated cirrhotic patients is not accurate. However, a model obtained by combining simple laboratory variables has a high sensitivity to predict CSPH in this population and may be useful to select the subset of patients requiring screening endoscopy. By this method, endoscopic screening could be obviated in about 40% of patients.
Color Doppler ultrasonography (CDUS) has been proposed as an alternative to portal pressure gradi... more Color Doppler ultrasonography (CDUS) has been proposed as an alternative to portal pressure gradient (PPG) measurement to detect transjugular intrahepatic portosystemic shunt (TIPS) dysfunction but with inconsistent results. This study aimed at developing and validating CDUS criteria to assess TIPS dysfunction. A total of 117 consecutive follow-up simultaneous CDUS and hemodynamic evaluations in 34 patients with TIPS were analyzed. TIPS dysfunction was defined as a PPG >12 mmHg. A predictive model was obtained with logistic regression and was validated in an independent, prospective sample of 119 consecutive paired CDUS/hemodynamic evaluations in 55 patients. TIPS dysfunction was present in 57 of the 117 studies in the retrospective series. At multivariate analysis, mean maximum flow velocity at the portal vein (mVPmax) and direction of flow in the intrahepatic portal vein branches (FD) were the only independent predictors of TIPS dysfunction. The prediction rule for TIPS dysfunction derived from the model (mVPmax <28 cm/s when flow is hepatofugal or mVPmax <39 cm/s when flow is hepatopetal) had 90% sensitivity, 45% specificity, and negative likelihood ratio of 0.23. This prediction rule was validated both in patients with bare stents and in patients with polytetra fluoroethylene (PTFE)-covered stents, showing an overall 87% sensitivity, 57% specificity, and 0.23 negative likelihood ratio. The combination of two CDUS parameters correlate with TIPS dysfunction with high sensitivity and low specificity but with a good negative likelihood ratio. TIPS catheterization can be safely avoided in half of the patients using this predictive rule.
European Journal of Gastroenterology & Hepatology, 2004
The haemodynamic changes induced by a meal on collateral vessels in portal hypertensive cirrhotic... more The haemodynamic changes induced by a meal on collateral vessels in portal hypertensive cirrhotic patients are not well characterized. We aimed to study the postprandial modifications of splanchnic circulation in patients with a patent paraumbilical vein (PUV). We studied 10 cirrhotic patients with patent PUV and 10 matched cirrhotic patients without PUV, by using echo colour Doppler at baseline and 15, 30 and 45 min after a standard mixed liquid meal (400 ml; 600 kcal). Calibre and blood flow velocities of the superior mesenteric artery, portal vein and PUV were obtained; congestion index of portal vein, portal blood flow, paraumbilical blood flow and effective portal liver perfusion were calculated; intrahepatic and intrasplenic arterial resistance and pulsatility indexes were recorded. We observed a postprandial splanchnic hyperaemia (superior mesenteric artery and portal vein blood flow increased after the meal in both groups; ANOVA P < 0.05), with no changes of hepatic impedance. In PUV patients, PUV constricted significantly postprandially, maximally at 30 min (calibre -17.5 +/- 7.0%; P = 0.003). Intrasplenic impedance, which may reflect portal pressure, increased, maximally at 30 min (pulsatility index +22.6 +/- 27.0%; P = 0.01), and inversely correlated with PUV vasoconstriction (R = 0.75, P = 0.01). In non-PUV patients intrasplenic impedance did not change. Portal liver perfusion increased similarly in both groups. PUV constricts after the meal, and this vasoconstriction is associated with an increase of splenic impedance which may indicate the postprandial increase of portal pressure observed in cirrhosis. The increase in postprandial portal liver perfusion in the PUV group is allowed by a paradox constriction of the collateral vessel.
Despite their relatively low prevalence, vascular diseases of the liver represent a significant h... more Despite their relatively low prevalence, vascular diseases of the liver represent a significant health problem in the field of liver disease. A common characteristic shared by many such diseases is their propensity to cause portal hypertension together with increased morbidity and mortality. These diseases are often diagnosed in young patients and their delayed diagnosis and/or inappropriate treatment can greatly reduce life expectancy. This article reviews the current body of evidence concerning Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia, cirrhotic portal vein thrombosis and other rarer vascular diseases including arterioportal fistulas. It also includes a section on the diagnostic imaging of vascular diseases of the liver and their treatment from a haematological standpoint (study of thrombotic diathesis and anticoagulation ther...
Portal hypertension is a severe, almost unavoidable complication of chronic liver diseases and is... more Portal hypertension is a severe, almost unavoidable complication of chronic liver diseases and is responsible for the main clinical consequences of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is currently the best available method to evaluate the presence and severity of portal hypertension. Clinically significant portal hypertension is defined as an increase in HVPG to >or=10 mmHg; above this threshold, the complications of portal hypertension might begin to appear. Measurement of HVPG is increasingly used in clinical hepatology, and numerous studies have demonstrated that the parameter is a robust surrogate marker for hard clinical end points. The main clinical applications for HVPG include diagnosis, risk stratification, identification of patients with hepatocellular carcinoma who are candidates for liver resection, monitoring of the efficacy of medical treatment, and assessment of progression of portal hypertension. Patients who experience a reduction in HVPG of >or=20% or to <12 mmHg in response to drug therapy are defined as 'responders'. Responders have a markedly decreased risk of bleeding (or rebleeding), ascites, and spontaneous bacterial peritonitis, which results in improved survival.
NCX-1000 (2(acetyloxy) benzoic acid-3(nitrooxymethyl)phenyl ester) is an nitric oxide (NO)-releas... more NCX-1000 (2(acetyloxy) benzoic acid-3(nitrooxymethyl)phenyl ester) is an nitric oxide (NO)-releasing derivative of ursodeoxycholic acid (UDCA), which showed selective vasodilatory effect on intrahepatic circulation in animal models of cirrhosis. This study was aimed at testing the efficacy and tolerability of this compound in patients with cirrhosis and portal hypertension. This was a single-center, phase-2a, randomized (4:1), double-blind, parallel-group, dose-escalating study. Patients received progressive oral doses of NCX-1000 or placebo up to 2 g t.i.d. or maximum tolerated doses for 16 days. Efficacy on fasting and postprandial hepatic venous pressure gradient (HVPG) at baseline and after treatment was assessed. Hepatic blood flow (HBF) and arterial blood pressure were also measured. Eleven patients (nine NCX-1000 and two placebo) were enrolled and completed the trial. After NCX-1000 treatment, HVPG did not change (16.7+/-3.8 vs. 17.1+/-3.8 mm Hg; P=0.596), and HBF decreased significantly (904+/-310 vs. 1,129+/-506 ml/min; P=0.043). The postprandial increase in portal pressure and HBF was not modified by NCX-1000. There was no significant effect on diastolic blood pressure, but systolic blood pressure was reduced by the treatment in a dose-dependent manner (121+/-11 mm Hg after NCX-1000 vs. 136+/-7 mm Hg at baseline; P=0.003). Seven non-serious adverse events were experienced by four patients (one on placebo). In patients with cirrhosis and portal hypertension, NCX-1000 administration was safe, but it was not able to reduce portal pressure. A significant reduction of systolic blood pressure and HBF was observed in the treatment arm, suggesting that the drug had systemic effects and lacked selective release of NO at the intrahepatic circulation.
Portal hypertension is a major cause of morbidity and mortality in liver cirrhosis. This article ... more Portal hypertension is a major cause of morbidity and mortality in liver cirrhosis. This article provides a background on the most important aspects of the evaluation of portal hypertension in patients with chronic liver diseases, with special attention to the measurement of portal pressure by hepatic vein catheterization. The rationale, technique, applications, costs, and limitations of measurements of the hepatic venous pressure gradient are thoroughly reviewed. Emerging, noninvasive methodologies for the evaluation of the patient with portal hypertension are also discussed.
The purpose of this article is to describe the Doppler waveform findings in the hepatic artery in... more The purpose of this article is to describe the Doppler waveform findings in the hepatic artery in the early posttransplantation period, both in the absence and presence of arterial complications. The presence of transient high-resistance Doppler waveforms in normal hepatic arteries is a common finding after grafting. Hepatic artery thrombosis and stenosis, and arterial steal syndromes can be diagnosed by Doppler in the early liver transplantation period.
We aimed to develop a model based on noninvasive variables for the prediction of clinically signi... more We aimed to develop a model based on noninvasive variables for the prediction of clinically significant portal hypertension (CSPH) and of esophageal varices (EV) in patients with compensated liver disease. Sixty patients with compensated liver cirrhosis diagnosed by histology were included in the training set. All patients had physical examination, laboratory tests, abdominal color-Doppler ultrasound, upper digestive tract endoscopy, and measurement of hepatic venous pressure gradient. Predictive models for the presence of CSPH and of EV were calculated. The models were validated in an independent series of 74 patients with compensated liver disease. Clinical and laboratory variables were selected in the final models, while ultrasonography did not add statistical power for the prediction of CSPH and EV. The model for prediction of CSPH included albumin, INR, and ALT. The best cutoff had 93% sensitivity and 61% specificity in the training set, and correctly classified 77% of patients in the validation set. Spider angiomas, ALT, and albumin predicted EV. The best cutoff of the model in the training set had a sensitivity of 93% and a specificity of 37% and correctly classified 72% of cases in the validation set. Noninvasive prediction of EV in well-compensated cirrhotic patients is not accurate. However, a model obtained by combining simple laboratory variables has a high sensitivity to predict CSPH in this population and may be useful to select the subset of patients requiring screening endoscopy. By this method, endoscopic screening could be obviated in about 40% of patients.
Color Doppler ultrasonography (CDUS) has been proposed as an alternative to portal pressure gradi... more Color Doppler ultrasonography (CDUS) has been proposed as an alternative to portal pressure gradient (PPG) measurement to detect transjugular intrahepatic portosystemic shunt (TIPS) dysfunction but with inconsistent results. This study aimed at developing and validating CDUS criteria to assess TIPS dysfunction. A total of 117 consecutive follow-up simultaneous CDUS and hemodynamic evaluations in 34 patients with TIPS were analyzed. TIPS dysfunction was defined as a PPG >12 mmHg. A predictive model was obtained with logistic regression and was validated in an independent, prospective sample of 119 consecutive paired CDUS/hemodynamic evaluations in 55 patients. TIPS dysfunction was present in 57 of the 117 studies in the retrospective series. At multivariate analysis, mean maximum flow velocity at the portal vein (mVPmax) and direction of flow in the intrahepatic portal vein branches (FD) were the only independent predictors of TIPS dysfunction. The prediction rule for TIPS dysfunction derived from the model (mVPmax <28 cm/s when flow is hepatofugal or mVPmax <39 cm/s when flow is hepatopetal) had 90% sensitivity, 45% specificity, and negative likelihood ratio of 0.23. This prediction rule was validated both in patients with bare stents and in patients with polytetra fluoroethylene (PTFE)-covered stents, showing an overall 87% sensitivity, 57% specificity, and 0.23 negative likelihood ratio. The combination of two CDUS parameters correlate with TIPS dysfunction with high sensitivity and low specificity but with a good negative likelihood ratio. TIPS catheterization can be safely avoided in half of the patients using this predictive rule.
European Journal of Gastroenterology & Hepatology, 2004
The haemodynamic changes induced by a meal on collateral vessels in portal hypertensive cirrhotic... more The haemodynamic changes induced by a meal on collateral vessels in portal hypertensive cirrhotic patients are not well characterized. We aimed to study the postprandial modifications of splanchnic circulation in patients with a patent paraumbilical vein (PUV). We studied 10 cirrhotic patients with patent PUV and 10 matched cirrhotic patients without PUV, by using echo colour Doppler at baseline and 15, 30 and 45 min after a standard mixed liquid meal (400 ml; 600 kcal). Calibre and blood flow velocities of the superior mesenteric artery, portal vein and PUV were obtained; congestion index of portal vein, portal blood flow, paraumbilical blood flow and effective portal liver perfusion were calculated; intrahepatic and intrasplenic arterial resistance and pulsatility indexes were recorded. We observed a postprandial splanchnic hyperaemia (superior mesenteric artery and portal vein blood flow increased after the meal in both groups; ANOVA P < 0.05), with no changes of hepatic impedance. In PUV patients, PUV constricted significantly postprandially, maximally at 30 min (calibre -17.5 +/- 7.0%; P = 0.003). Intrasplenic impedance, which may reflect portal pressure, increased, maximally at 30 min (pulsatility index +22.6 +/- 27.0%; P = 0.01), and inversely correlated with PUV vasoconstriction (R = 0.75, P = 0.01). In non-PUV patients intrasplenic impedance did not change. Portal liver perfusion increased similarly in both groups. PUV constricts after the meal, and this vasoconstriction is associated with an increase of splenic impedance which may indicate the postprandial increase of portal pressure observed in cirrhosis. The increase in postprandial portal liver perfusion in the PUV group is allowed by a paradox constriction of the collateral vessel.
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